Inflicted childhood neurotrauma (ICN) - traumatic brain injury due to child abuse - is the leading cause of death from traumatic brain injury (TBI) in children less than 2 yrs of age. Recognition of ICN can be difficult and misdiagnosis is common. Accurate and timely diagnosis of ICN is of critical importance; infants with ICN who are misdiagnosed are likely to return to a violent environment and be re-injured or killed. There are currently no evidence- based strategies or tools to screen for ICN. The long-term objective of this research is to create an evidence-based approach to evaluating infants at high-risk of ICN. Over the past four years, we have demonstrated that increases in the serum concentrations of two brain- specific biomarkers - neuron specific enolase and myelin basic protein - are sensitive and specific for brain injury and may be able to be used as a screening tool for ICN. We have also derived a sensitive and specific clinical decision rule (CDR) for predicting ICN using easily measured clinical and laboratory variables. The specific aims of the current proposal are (1) to perform a two-site, prospective definitive study to evaluate the use of serum biomarkers to screen for ICN in high-risk infants (2) to improve the sensitivity and specificity of biomarkers for detection of ICN by creating biomarker profiles using a combination of multiplex bead technology and conventional two-dimensional difference in gel electrophoresis/mass spectroscopy (3) to validate prospectively the previously derived CDR and to compare the accuracy of the CDR alone to the CDR in combination with biomarkers. If these tools are effective for screening for ICN, they would be instrumental in decreasing morbidity and mortality from the leading cause of death from child abuse. Relevance to public health: Inflicted childhood neurotrauma (ICN) - often referred to as shaken baby syndrome - is the leading cause of death from child abuse. Proper diagnosis is essential in order to avoid returning an injured child to a violent environment where he or she may be re-injured or killed. This study evaluates two ways to screen for ICN: by measuring the levels of certain chemicals in the blood and by combining certain laboratory and clinical information into a clinical decision rule. By improving evaluation and diagnosis of ICN, we will be able to decrease morbidity and mortality from this devastating type of child abuse. PUBLIC HEALTH RELEVANCE: Shaken baby syndrome is the leading cause of death from child abuse. Many children who die of shaken baby syndrome have been shaken previously by a caretaker but their symptoms (e.g. vomiting or irritability) are misdiagnosed by a medical professional. The misdiagnosis allows them to return to a violent home where they are re-injured. The goal of our study is to find ways to help doctors identify shaken baby syndrome when it initially presents before children are re-injured and/or killed.